Biomedical subjects

S A Rude

Publications and source records attributed to S A Rude.

9 recordsLinked to original sources

PubMed2000

The effect of gravity on the horizontal and vertical vestibulo-ocular reflex in the rat.

Horizontal and vertical eye movements were recorded in alert pigmented rats using chronically implanted scleral search coils or temporary glue-on coils to test the dependence of the vestibulo-ocular reflex (VOR) upon rotation axis and body orientation. The contributions of semicircular-canal versus otolith-organ signals to the VOR were investigated by providing canal-only (vertical axis) and canal plus otolith (horizontal axis) stimulation conditions. Rotations that stimulated canals only (upright yaw and nose-up roll) produced an accurate VOR during middle- and high-frequency rotations (0.2-2 Hz). However, at frequencies below 0.2 Hz, the canal-only rotations elicited a phase-advanced VOR. The addition of a changing gravity stimulus, and thus dynamic otolith stimulation, to the canal signal (nose-up yaw, on-side yaw, and upright roll) produced a VOR response with accurate phase down to the lowest frequency tested (0.02 Hz). In order to further test the dependence of the VOR on gravitational signals, we tested vertical VOR with the head in an inverted posture (inverted roll). The VOR in this condition was advanced in phase across all frequencies tested. At low frequencies, the VOR during inverted roll was anticompensatory, characterized by slow-phase eye movement in the same direction as head movement. The substantial differences between canalonly VOR and canal plus otolith VOR suggest an important role of otolith organs in rat VOR. Anticompensatory VOR during inverted roll suggests that part of the otolith contribution arises from static tilt signals that are inverted when the head is inverted.

Animals↗

PubMed1998

Chronic recording of the vestibulo-ocular reflex in the restrained rat using a permanently implanted scleral search coil.

A technique is described which allows accurate long-term monitoring of eye movements in the rat using permanently implanted scleral search coils. Search coils permanently sutured around the sclera yield vestibulo-ocular reflex (VOR) gain and phase values which are comparable to those reported previously in the literature using acutely implanted coils or electrooculographic electrodes. Considerations related to strain, sex and surgical procedures which permit measurement of responses in the chronically restrained rat are described. VOR gain and phase show a time course to their recovery following the implant surgery, with asymptotic performance typically attained approximately 10 days post-surgically. This technique, with the ability to monitor eye movements over weeks to months, appears ideal for development of rodent models of reflex adaptation which require observation of reflex behavior over extended periods of time. Development of a chronic procedure for monitoring eye movement in rodents is especially important given their initial response to restraint (extensive struggling). Finally, adaptation of this technique to smaller species (e.g., mouse) appears technically feasible which should permit the application of transgenic and knockout techniques to the determination of various vestibular reflex functions requiring long-term monitoring.

Animals↗

PubMed1998

Alterations in rat horizontal vestibulo-ocular reflex phase as a function of orientation in gravity.

The effect of changes in static and dynamic gravity signals on the phase accuracy of the horizontal vestibulo-ocular reflex (HVOR) was studied in rats using chronically implanted scleral search coils to monitor eye movements. Rats were sinusoidally rotated using a range of different frequencies (0.035-2 Hz) in a plane which always activated the horizontal semicircular canals but in one of three different orientations with regard to gravity which differentially activated the otolith organs: 1) upright-normal static gravity signal, no dynamic otolith activation; 2) inverted-inverted static gravity signal, no dynamic otolith activation; 3) on-side-dynamic activation of the otolith organs. In the upright orientation, the HVOR shows a phase advance at 0.2 Hz and below but not at 0.5 Hz and above. Phase accuracy of the HVOR was further degraded in the inverted orientation with rats showing large phase leads at 0.2 Hz and below. In contrast, accuracy of the HVOR was significantly improved at 0.2 Hz and below in the on-side orientation with phase accurate eye movements down to the lowest frequency tested. The results further support the idea that otolith organs play an important role in VOR generation by supplementing the semicircular canals' response to angular head movements.

Animals↗

PubMed1996

Otolith orientation and downbeat nystagmus in the normal cat.

Upward drift of the eyes in darkness, influenced by whole body orientation, was studied in 12 cats using electromagnetic search coil and electro-oculographic techniques. Animals were positioned stationary with respect to gravity with 0 degree tilt ("upright") or rolled 90 degrees ("on side"), pitched 90 degrees ("on nose" or "on tail"), or inverted 180 degrees ("upside down"). A downbeat quick-phase nystagmus (slow-phase upward in the cat's orbit) was measured, varying in magnitude with angle of tilt (0.21 degree/s at 0 degree tilt; 4.14 degrees/s at 180 degrees tilt). The drift was not present in the light. Upward eye velocities over a range of body orientations in darkness suggest a systematic drive to the eyes which increases with tilt away from upright. The relationship of this behavior to previous models of angular velocity estimation by an otolith-driven central mechanism is discussed.

Animals↗

PubMed1991

Frequency dependence of cat vestibulo-ocular reflex direction adaptation: single frequency and multifrequency rotations.

Vertical and horizontal vestibulo-ocular reflex (VOR) eye movements were recorded in alert cats during horizontal rotation in total darkness before and after a 2 h vestibulo-ocular reflex direction adaptation procedure. Adaptation stimuli were whole body horizontal vestibular rotation coupled to synchronous vertical optokinetic motion. The waveform of the adaptation stimuli was either a sinusoid at 0.05, 0.1, 0.25, 0.5, or 1 Hz, or a sum of sinusoids containing 0.2, 0.3, 0.5, 0.7, 1.1, and 1.7 Hz. Exposure to single frequency stimuli produced adaptive vertical VOR with a gain that was greatest near the training frequency; adaptive VOR phases were advanced below, accurate at, and lagged above the training frequency. Exposure to the multifrequency waveform produced a uniform modest increase in gain across frequencies, with accurate adaptive VOR phase.

Acclimatization↗

PubMed1988

Dynamic otolith stimulation improves the low frequency horizontal vestibulo-ocular reflex.

The horizontal vestibulo-ocular reflex was measured electro-oculographically in four cats during sinusoidal rotations in the dark at frequencies from 0.01 Hz to 1.0 Hz in five body orientations. Vertical axis rotations in the prone and supine positions were used to stimulate horizontal canals only. Horizontal axis rotations, with the cat on the left or right side or nose down (pitched 90 degrees from prone) were used to stimulate horizontal canal plus otolith organs. At frequencies below 0.05 Hz the horizontal vestibulo-ocular reflex produced by horizontal canal plus otolith stimulation showed a more accurately compensatory response than the horizontal vestibulo-ocular reflex produced by horizontal canal stimulation alone. Canal plus otolith horizontal vestibulo-ocular reflex gain and phase remained relatively constant across all frequencies, while the horizontal vestibulo-ocular reflex gain and phase from orientations involving canal stimulation alone changed dramatically as rotation frequency decreased. In addition, the reflex in the supine position showed gain decreases and phase advances at higher frequencies than in the prone position.

Animals↗

PubMed1987

Simultaneous opposing adaptive changes in cat vestibulo-ocular reflex direction for two body orientations.

The specificity of adaptation of vestibulo-ocular reflex direction was examined by exposing cats to combined pitch vestibular rotation and horizontal optokinetic motion at 0.25 Hz, while alternating body position between lying on the left side and lying on the right. The direction of optokinetic motion relative to head motion was reversed when the cat's body posture was changed so that, for example, if head upward rotation was coupled to leftward visual world motion when the cat was lying on its left side, then head upward rotation was coupled to rightward visual world motion when the cat was on its right side. Body position and optokinetic motion direction were changed every 10 min for a total of 2 h of adaptation on each side. Horizontal and vertical electrooculographic recordings were made during pitch rotations in darkness before and after adaptation. Saccades were removed from the records and vestibulo-ocular reflex gain was measured in the direction of optokinetic motion. In every case, the adaptation procedure produced a directional change in the vestibulo-ocular reflex specific to the posture during measurement and appropriate to reduce the retinal image motion caused by the combined vestibular and optokinetic stimuli. That is, adaptive horizontal eye movements measured on the two sides were in opposite directions for the same direction of head motion. This specificity suggests that adaptation of vestibulo-ocular reflex direction involves specific neural pathways that are controlled by body orientation signals which most likely arise from the otolith organs.

Adaptation, Physiological↗

PubMed1986

Inactivation of leukocyte elastase by aryl azolides and sulfonate salts. Structure-activity relationship studies.

The inhibitory activity of a series of aryl azolides and sulfonate salts toward human leukocyte elastase is reported. Several of the compounds were found to be potent inhibitors of the enzyme. Active compounds were obtained only when the specificity group and the reactive moiety were separated by a two-carbon chain. The introduction of hydrophobic groups enhanced the inhibitory activity of these compounds, with the exception of the sulfonate salts. The nature of the leaving group had a profound effect on inhibitory activity, with compounds 23 and 26 being the most active (kobsd/[I] = 11,722 and 13,500 M-1 s-1, respectively).

Azo Compounds↗

PubMed1985

Amino acid derived latent isocyanates: irreversible inactivation of porcine pancreatic elastase and human leukocyte elastase.

Several amino acid derived azolides (I) have been synthesized and investigated for their inhibitory activity toward human leukocyte elastase and porcine pancreatic elastase. The inhibitory activity was found to be dependent on the nature of the precursor amino acid ester. Thus, compounds derived from L-valine methyl ester 3, L-norvaline methyl ester 5, DL-norleucine methyl ester 9, and L-methionine methyl ester 10 were found to inhibit irreversibly both enzymes. Compound 10 was found to be a specific and selective inhibitor of human leukocyte elastase. In contrast to these, inhibitors derived from glycine methyl ester 1, D-valine methyl ester 4, and D-norvaline methyl ester 6 were found to be inactive. The results of the present study show that latent isocyanates derived from appropriate amino acids can serve as selective inhibitors of serine proteases and are of potential pharmacological value.

Amino Acids↗